The role of pharmacokinetics (PK) and pharmacodynamics (PD) has increased dramatically as anticancer drug discovery and development has shifted towards molecularly-targeted therapies. Increased appreciation of PKJPD relationships has resulted in increased emphasis on generating and analyzing such data, even for agents without defined molecular targets. Increased recognition of drug-drug interactions and pharmaco-genetic differences in drug metabolism, disposition, and susceptibility has increased the need for assays to define relevant polymorphisms and their clinical impact. The Clinical Pharmacology Analytical Facility (CPAF) was established in 1994 to provide state-of-the-art pharmacology research facilities for the University of Pittsburgh Cancer Institute (UPCI). The CPAF relocated in September 2002 to 1,000 square feet of laboratory space in the Research Pavilion of the Hillman Cancer Center. The CPAF supports preclinical and clinical pharmacology research programs. Services include quantitation of drugs, metabolites, and other materials; identification of metabolites; and PK and PD analyses of anticancer agents that are undergoing clinical trials at UPCI. The CPAF also phenotypes and genotypes cytochrome P450 isoforms and other key drug-metabolizing enzymes. It provides important consultative services to UPCI investigators, on the design of pharmacologic studies and drug assay, metabolism, and PK analyses. The CPAF is directed by Dr. Merrill J. Egorin, with input from Dr. Robert Bies. The Facility is overseen by an advisory committee, representing the Schools of Medicine and Pharmacy, and the Biostatistics Facility. During the past year, the CPAF has provided support for 29 clinical trials at UPCI, 14 CTEP-sponsored clinical trials at other NCI-designated cancer centers, and 54 animal pharmacology projects. It also provided analytical chemistry support for 3 in vitro, pharmacology studies. To expand its capabilities and increase its value, the CPAF has enhanced substantially its analytical chemistry instrumentation, its PK modeling software, and its personnel. The Facility has acquired two LC/MS instruments and an LC/MS/MS. The CPAF was recognized by Pharsight Corporation as a Center of Pharmaeokinetic Excellence, thereby allowing it to implement sophisticated software. The requested CCSG funding will support Facility personnel for their efforts in providing consultative services related to assay development, methodology, protocol design, and data interpretation, and their efforts in ensuring that instrumentation and software are suitably maintained and available for application to projects by investigators seeking support from the Facility.